The Kiwi Ketogenic study

Being a patriotic ‘kiwi’, I am always very pleased to write about interesting Parkinson’s research originating from the homeland. And recently the results of an interesting clinical study that was designed and conducted in New Zealand have been published.

The clinical study was focused on whether a diet manipulation could influence motor and non-motor symptoms/features of Parkinson’s.

Specifically, the researchers were looking at the low-fat versus ketogenic diets.

In today’s post, we will discuss what is meant by a ketogenic diet, we will assess the results of the study, and consider what they might mean for the Parkinson’s community.

Aotearoa (also known as New Zealand) is a remarkable little country (and yes, I know I’m slightly biased).

It flies under the radar for most folks who are not interested in rugby, amazing scenery, great quality of life, or hobbits, but historically this tiny South Pacific nation of 4.6 million people has punched well above its weight on many important matters.

For example, on the 19th September 1893, the governor, Lord Glasgow, signed a new Electoral Act into law. And as a result of that simple act, New Zealand became the first self-governing country in the world in which all women (over the age of 21) had the right to vote in parliamentary election (Australia followed in 1902, the US in 1920, & the Britain in 1928). That achievement, it should be said, was the result of years of dogged effort by suffrage campaigners, led by Kate Sheppard who is today acknowledged with her portrait on the $10 note:

A New Zealander made the first trans-global radio transmission on the 18th October 1924. Invalided during WWI, Frank Bell revived his childhood interest in wireless communication, and after being the first kiwi to have two-way radio contact with Australia and North America, he achieved something far more impressive. From the family sheep station in ‘Shag Valley’ (East Otago – bottom of the South Island), he sent a Morse code transmission (“Greetings from New Zealand, signed Bell Z4AA”) which was received and replied to by amateur operator Cecil Goyder at Mill Hill School (London).

New Zealand was also where jet boats was first invented by Sir Bill (William Hamilton). His first jet boat was a 3.6 meter (12 foot) plywood hull with a 100 E Ford engine, and the jet a centrifugal type pump. This craft was tested on the Irishman Creek dam, before it ran successfully upriver in 1953. And from there it kind of went viral. In 1960, three Hamilton jet boats (the Kiwi, Wee Red and Dock), became the first and only boats to travel all the way up through the Grand Canyon.

And the list doesn’t stop there. We could go on with other great firsts:

Sir Ed (Hillary) – first to summit Everest (to be fair, it was a team effort)

Sir Ernest (Rutherford) – first to split the atom

Sir Peter (Blake) – first to sail around the world in less than 75 days (again, a bit of a team effort)

Sir John (Walker) – first to run the mile in under 3:50 (now a member of the Parkinson’s community)

Georgina Beyer – first openly transsexual mayor, and then the world’s first openly transsexual Member of Parliament

AJ Hackett & Henry van Asch – set up the first commercial bungy jump on the Kawarau Bridge, near Queenstown

Helen Clark, Dame Siliva Cartwright & Sian Elias – first country to have women in the top three senior public roles (Prime Minister, the Governor General, & the Chief Justice, respectively)

Rocket Lab – first private company in the Southern Hemisphere to reach space (in 2009)

And I guess we better stop there (if only out for fear of making larger nations feel somewhat inadequate), but you get the idea – small nation, doing lots of great stuff.

There is also a very proactive Parkinson’s community – with groups like Parkinson’s New Zealand organising and running support groups across the country, and helping to fund some of the great local Parkinson’s research.

And some of that local Parkinson’s research has been discussed previously on this website (Click here, here and here for examples of previous posts), and it is also the focus of today’s post:

Recently the results of an interesting nationwide demographics study were published:

The researchers who conducted this study had previously used data extracted from the national Pharmaceutical Collection of community‐dispensed medications to describe the prescribing patterns of anti-Parkinsonian medications in New Zealand (Click here to read that study). They had also recently published an incidence assessment for New Zealand – with 210 cases per 100 000 member of the general population (based on 2013 data – Click here to read more about that).

In this current study, the researchers collected information on Parkinson’s‐related medications from the national Pharmaceutical Collection of community‐dispensed medications (for the period January 1, 2005, to December 31, 2014) and they also determined Parkinson’s diagnoses independently via national mortality and hospital admissions data sets. Of the total number of people (33,917) identified by the medication analysis, 42% (14,179) also had a ICD‐10 diagnostic codes listed in the national databases. And 763 of those people had a Parkinson’s diagnosis.

Ok, and what did they do with that data?

The researchers were interested in whether the prevalence of Parkinson’s was the same across all of the different ethnic groups living in New Zealand.

And is it?

Well, according to data collected from the 2013 census, 15% of the population identified as Māori (the ingenious Polynesian people of Aotearoa, who arrived 4-500 years before the Europeans – Source), 74% as Pākehā (or European), 12% as Asian, 7% as Pasifika (from one of the Polynesian Pacific island nations), and 1.2 % as Middle Eastern/Latin American/African.

And this is where the study gets interesting:

The 2013 age‐standardised prevalence (per 100,000 population) for European was 223. For individuals of an Asian heritage, it was 174. For the Pasifika population, the prevalence of Parkinson’s was 160 per 100,000 (are you starting to notice a trend yet?); and for the Māori community, the prevalence was just 114.

Read that paragraph again if you are not yet surprised.

The prevalence of Parkinson’s in individuals of a Māori background was almost 50% less than that of the Pākehā (Europeans)!

This lower incidence of Parkinson’s in Māori and Pasifika, is particularly curious as there is a high prevalence of type 2 diabetes in these two communities (Click here to read more about this) – which is a condition generally associated with an increased risk of Parkinson’s (Click here to read a previous SoPD post on this).

But this lower incidence of Parkinson’s trend is also observed in other medical conditions, such as multiple sclerosis. Māori have a low frequency of genetic mediators of multiple sclerosis risk (Click here to read more about this), and they also appear to be 3 times less likely to be diagnosed with that condition than non-Māori individuals (Click here for more on this).

Interesting. So summing up, what does it all mean?

No wait. We’re not finished yet.

That wasn’t the only interesting piece of Parkinson’s research out of New Zealand recently. Far from it.

The results of the ‘Nutrition in Parkinson’s‘ study have just been published and they make for some interesting reading.

What is the ‘Nutrition in Parkinson’s’ study?

The ‘Nutrition in Parkinson’s’ study was a clinical pilot study conducted at Waikato Hospital in Hamilton (New Zealand). It was conducted June to August 2017, and it involved 47 people with Parkinson’s being randomly divided into two groups and being placed on two very different diets.

The study was coordinated by neurologist Dr Matthew Philips – who has provided a very useful video explaining not only an overview of the study, but all aspects of Parkinson’s in general (recommended viewing – very thorough and easy to follow):

Dr Phillips also provides useful, down-loadable reading material on many different aspects of Parkinson’s – click here to read more about that.

The 47 individuals enrolled in the study were randomly placed on one of two diets:

A low-fat diet

A Ketogenic diet

Ok, I think I can figure out what a low-fat diet is, but what is a Ketogenic diet?

The original Ketogenic (or simply Keto) diet was a high-fat, adequate-protein, and low-carbohydrate mix. It is used in medicine primarily to treat children with difficult-to-control epilepsy. There are now many different versions of this diet, but they are all based on a same basic idea: In the absence of carbohydrates, the Keto diet forces the body to use fat to generate ketone. (More on ‘ketones’ in a minute)

In the modern western world, our diets are very high in carbohydrates, and our bodies find this situation very agreeable. The carbohydrates contained in food are easily converted into glucose, which can be transported around the body or stored, providing a ready supply of energy (which is particularly important in fueling our particularly energy hungry brains).

The problem with this high carbo situation, however, is that in our modern western world we are also becoming more and more sedentary – sitting at desks at work or lying around consuming media. And as a result, the converted glucose is not being burned up, but rather stored as fatty deposits around our bodies.

And this is where the Keto diet can come into play.

On the Keto diet, when there is little carbohydrate intake, the liver converts those fat deposits into fatty acids and ketone bodies.

What are ketone bodies?

Ketone bodies (or simply ketones) are three water-soluble molecules produced by the liver during ketogenesis. There are three ketone bodies – acetoacetate, beta-hydroxybutyrate, and acetone:

Ketones act primarily as a source of energy for cells – particularly the brain – in the absence of glucose. After the 3 days on a low glucose diet, the brain will get approximately 25% of its energy from ketone bodies, and this will shift to 70% after 4 days (Source).

But there is also evidence that ketones might be neuroprotective (Click here for a review on this topic).

Ketone bodies have a characteristic smell – often described as ‘fruity’ or ‘like nail polish remover’. You can easily smell a change of breath in people on a Keto diet, and this ‘breath test’ is an easy indication of whether an individual is on a Keto diet.

In this study, the investigators found that the infusion of the ketone body d-beta-hydroxybutyrate in mice that had been injected with a neurotoxin (MPTP), improved mitochondrial function and reduced the loss of dopamines and associated motor deficits. The researchers concluded that given “the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier” d-beta-hydroxybutyrate could “be a novel neuroprotective therapy for PD”.

This result is similar to what other research groups have found in models of Parkinson’s (Click here and here to read more about this). Perhaps more research in this area could be useful (but it should be noted that the half-life of ketones is very short).

And the study being reviewed in this post is not the first time that a Keto diet has been tested in people with Parkinson’s:

In this small pilot study, the investigators recruited 7 people with Parkinson’s. Five of these volunteers completed the study and were able to prepare a “hyperketogenic” diet at home for the entire 28 day study. Parkinson’s clinical (UPDRS) scores improved in all of the 5 participants during the study, but given that they were not blind to the treatment, a placebo effect can not be ruled out.

So what did the people in the new ‘Kiwi’ Keto diet study have to do?

During a two week period before the study started, the participants were assessed twice by clinicians (recording weight, blood pressure, clinical exam scores, blood, etc). These measures were the ‘baseline’ recordings of the study – a measure of the participants before starting the treatment that could be used for comparative sake at the end of the study. They were also given a glucose/ketone monitor (Freestyle Neo; Abbott Diabetes Care) to keep track of and assess their ketone levels.

After the baseline assessments, the participants were then given their dietary instructions:

The keto diet plan offered participants with the same amount of energy (1,750 kcal per day), but was composed of 152 g of fat (67 g saturated), 75 g of protein, 16 g net carbohydrate, and 11 g of fiber.

Both groups were offered “caloriebooster” recipes for those with higher energy needs. But these differed in that the low fat caloriebooster contained 4 g of fat (1 g saturated), 6 g of protein, 102 g net carbohydrate, and 13 g of fiber, while the Keto diet caloriebooster contained 50 g of fat (22 g saturated), 6 g of protein, 5 g net carbohydrate, and 4 g of fiber. Each caloriebooster provided on average 500 extra kcal.

Importantly, all of the ingredients for the meal plans could be purchased at local supermarkets. If you would like to see the meal plans for both groups, Click here and then scroll to the bottom of the page and click on ‘Supporting information’ where you can access supplementary information, including the standard diet plans.

NOTE: In an interesting step, the investigators have also made available all of the information and videos about the diets on the patient portal, if you are interested in having a look (Click here to see more).

The participants then commenced their individual meal plans and they maintained them for 8 weeks. At 4 and 8 weeks into the diet, they were assessed again by the clinicians.

And what did they find in the results?

Encouragingly, the results show that both group were able to stick to their modified diet for 8 weeks. And the high retention rate was helped by an innovative approach from the investigators of providing weekly videos and emails every 2 days.

The high retention rate was also impressive given the daily use of the blood glucose and ketone monitors. Many previous Keto studies have relied on urine monitors for reading of ketone levels, but these are not considered as reliable as the blood monitors.

The results also show that the keto diet is safe and well tolerated in people with Parkinson’s.

But what did the results show about the Parkinson’s symptoms?

The results showed that both diet groups had decreased scores in their MDS-UPDRS assessments at 8 weeks compared to their baseline recordings.

What does that mean?

The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (or MDS-UPDRS) is one of the most widely used clinical measures of Parkinson’s. It is made up of 5 parts, which assess different aspects of the condition. A decrease in the MDS-UPDRS score suggests improvement in Parkinson’s symptoms, while an increase indicates disease progression.

Compared to the UPDRS scores at the start of the study, both groups showed improvements in their measures (that is to say, both groups had reductions in their scores).

Interestingly, the ketogenic diet group exhibited a significant decrease in their Part I score (−4.5 points improvement in baseline scores) compared to the low-fat group (−0.99 points). Part I concerns ‘‘non-motor experiences of daily living’’, and the largest between-group difference were recorded for urinary problems, pain, fatigue, and cognitive impairment (many of the most problematic aspects of Parkinson’s in terms of quality of life). No differences were observed between the two diet groups in the other four parts of the UPDRS. It will be interesting to see if this improvement in Part I score is replicated in other Keto studies in Parkinson’s.

Adherence to the diets looks rather good as the low-fat diet group showed decreases in HDL, LDL, total cholesterol, and urate levels, while the ketogenic group showed increases.

The most common negative (or ‘adverse’) effects mentioned by the participants was “excessive hunger in the low-fat group” and “intermittent exacerbation of the PD tremor and/or rigidity” in the ketogenic group.

And this is another interesting result from the study, for anyone with Parkinson’s considering the keto diet. The intermittent exacerbation of the PD tremor/rigidity actually resulted in two participants withdrawing from Keto group at the end of week 1. But this adverse effect appears to have only been a transient phenomenon as it improved in the remaining subjects from weeks 5 to 8. It will be interesting to see if this effect is also replicated in follow up Keto studies in Parkinson’s.

So we should all rush off and jump on a Keto diet?

The study has demonstrated that is “it is plausible and safe to maintain a low-fat or ketogenic diet for 8 weeks”.

But the researchers admit in their discussion that the study is very small, and a larger study and longer diet intervention is required for any solid conclusions to be made. In addition, there was no control group in this study, and the participants were not ‘blind’ (everyone knew that they were on a special diet) – thus a placebo effect could have been in affect. The investigators tried to limit this by blinding the clinicians who conducted the movement assessments, but the participants still knew that they were being treated. And given the change in smell of one’s breath, I am having a hard time imagining how ‘double blind’ clinical testing of the Keto diets could be achieved. It will probably be rather difficult.

Then there is also the possibility of an L-dopa effect.

As both of the diets were moderate-low in protein, it could be positively affecting the availability of the main Parkinson’s treatment, L-dopa. Protein usually interferes with the absorption of L-dopa in the gut. Thus, some benefits observed in this study could perhaps simply be attributed to improved L-dopa absorption rather than any other effect. The researchers tried to counter this by making sure that participants were getting a minimum level of protein to reduce this possibility, but a larger study will be required to better assess whether this effect had any role in the results.

Are there any dangers with a keto diet?

It should firstly be noted that ketogenesis occurs constantly in healthy individuals. It is a natural process.

Second, as with all things in life, there is a balancing act to ketogenesis.

The overproduction of ketone bodies can lead to a state known as ketoacidosis – excessively high levels of ketones. And this can be common in individuals with diabetes or glucose intolerance (PLEASE NOTE: as we have discussed before, glucose intolerance appears to be present in more members of the Parkinson’s community than the general public – click here to read a previous post on this topic).

Insulin is a protein (actually a hormone) that our body makes, which allows our cells to use glucose as a source of fuel. After eating food, our body releases insulin which then attaches to cells and signals to those cells to absorb the glucose from our bloodstream. Without insulin, our cells have a hard time absorbing glucose. In case of diabetes or insulin deficiency, the cells in your body do not respond adequately to normal levels of insulin. This results in a build up of glucose in the blood, and the cells seeking an alternative source of energy… (can you guess where they find that energy?)

The body produces high levels ketone bodies as a result of not enough glucose accessing cells. But the ketones acetoacetate and beta-hydroxybutyrate are both acids, and when they start to build up and bodily fluids become too acidic, some of the body’s systems stop functioning properly. This is ketoacidosis and it can be dangerous – so please discuss any changes in your diet with your physician before attempting anything.

In addition, as we discussed above, changes in protein levels in one’s diet can affect the absorption of L-dopa, so (again) please discuss any changes in your diet with your physician before attempting anything.

So what does it all mean?

I have had a lot of readers previously ask about the Keto diet and whether it can help in Parkinson’s, so it brought me great pleasure when I heard about the ‘Nutrition in Parkinson’s’ study that Dr Philips and his team were conducting in New Zealand (Thanks Dilys). While it is difficult to draw too many conclusions from the results of the study, it is encouraging to see researchers addressing the topic.

Many members of the community experiment with various aspects of diet because (like exercise) it is one aspect of their treatment that they feel like they can control/influence. This is empowering, but it needs to be supported by the research community with some carefully designed and conducted studies.

Given the very interesting results that the current study have produced (the significant improvement in UPDRS Part I scores compared to the low fat diet group and the transient exacerbation of Parkinson’s tremor/rigidity at commencement), it would be very encouraging to see a much larger and longer clinical trial of the ketogenic diet in Parkinson’s, which could more thoroughly investigate these findings.

And it would be particularly encouraging if that larger clinical study were to be conducted in a particular South Pacific nation.

I’m just saying.

EDITORIAL NOTE: The information provided by the SoPD website is for information and educational purposes only. Under no circumstances should it ever be considered medical or actionable advice. It is provided by research scientists, not medical practitioners. Any actions taken – based on what has been read on the website – are the sole responsibility of the reader. Any actions being contemplated by readers should firstly be discussed with a qualified healthcare professional who is aware of your medical history. Dietary changes can impact the effectiveness of treatments. PLEASE speak with your medical physician before attempting any change in an existing treatment regime.

Simon, this is a v. interesting post and indeed a bit of a muse on New Zealand. I enjoyed reading it. When I began the post I wondered whether the lower incidence of Parkinson’s in Māori and Pasifika, where there is also a high prevalence of type 2 diabetes (a condition generally associated with an increased risk of Parkinson’s) could be due to medication to treat the type 2 diabetes, notwithstanding what dietary reasons may be at play. Naturally I am referring to the interesting results of those trialing Victoza and other injectable type 2 diabetes medications who are seeing improvement in PD symptoms. Was medication considered in this trial?

Hi Pamela,
Thanks for your interesting comment – the short answer is I’m really not sure. In the discussion of the report, the researchers focus more on the possibility of a genetic difference (possibly genetic variants that infer a reduced risk of developing Parkinson’s), as well as the heavy urbanisation of the maori community – possibly reducing their exposure to pesticides, etc. The long answer to your question is I’m not sure anyone knows.
For readers not familiar with it, Victoza is also called Liraglutide (a GLP-1 agonist used in the treatment of diabetes). It is a similar type of drug to Exenatide which had interesting phase II clinical trial results in Parkinson’s last year.
Kind regards,
Simon

Hi Simon,
And may I just wander off the rails for a minute to apologise for having been quiet the last couple of months (I have been getting ready for our big forum and helping here and there with people writing up projects etc.). Hey, maybe a lot of readers have not missed my long rambles through Parkydom!
Okay, to the serious point of this e-mail; this article was a pleasure to read as sensible study criteria provided very interesting outcomes focused on macro-nutrients – of course as you have pointed out there is a degree of ambiguity in the study (the amount of protein being very middle-ground leaves us none the wiser as to whether blood/brain competition with PD drugs is a definite factor or not). The other main point: It’s not a double-blinded study but I agree with you how can such a study be engineered? I have tried ketone diets in the past and always noticed ‘onion breath’ after a few days which was the tip-off that it was working.

Right, no rambling other than to say all the forum delegates will receive a welcome file with various printouts and one of the printouts will include ‘must-reads’ and your blog will be at the top of the list. I have always believed in giving credit where credit is due and your blog should be mandatory reading for any that are seriously wanting to keep up with PD research.

First off the study you quote was investigating seizures and not neurological disorders. Second, I believe the study has a tragic flaw in logic that is common in biology research today. When x is present y is present. This in NOT proof x causes y. I realize that gut microbia is a popular topic today, but it is a parallel indicator and not a causative effect. I have a real disease and should be using a walker, and I am not. I am living proof of my theories.

Hi Joseph, I agree correlation does not = causality. I was simply mentioning one gut/CNS axis (seizures) where the Keto diet is apparently accepted, and there are microbiome changes, to raise a question; not a statement. Indeed the paper you quote has a question for the title. Most science starts with questions and hypotheses, not certainties.

Hi Simon,
Thank you for the links to Dr. Matthew Phillips’s pdf material on Parkinson’s. I downloaded a number of the pdfs, and the material is well written and curated, accessible to the layperson, and was good learning material for a relative newbie like myself.
I also had a momentary urge to move to New Zealand after reading this post – such an inspiring history of trailblazing, thank you. The humanity of the current NZ PM is a breath of fresh air on the international stage as well, and this is obviously not an outlier.